PROGRAM KBKPROGRAM KBK

FK-UKIFK-UKI

INFERTILITY HORMON DISORDER

Prof. Dr. drh. Maria Bintang, MS

GURU BESAR BIOKIMIA

REFERENCESREFERENCES American society for reproductive medicine. 2008. American society for reproductive medicine. 2008. Canadian Family Physician VOL 38: February 1992 Endocrinology. Vol. 142, No. 10 4272-4281. 2001Endocrinology. Vol. 142, No. 10 4272-4281. 2001 Journal of Lipid Research, Vol. 44, 154-163, January 2003 Journal of Lipid Research, Vol. 44, 154-163, January 2003 JCPSP, Vol. 17 (4): 191-194. 2007 J Obstet Gynecol India Vol. 56, No. 1 : January/February 2006 Lehninger. 2000. Lehninger. 2000. Principles of biochemistryPrinciples of biochemistry 3rd Ed. 3rd Ed. Michael W. KingMichael W. King. 2006. . 2006. Medical BiochemistryMedical Biochemistry.. Murray R K, Granner D k, Mayers P a & Rodwell V w. 2003. Murray R K, Granner D k, Mayers P a & Rodwell V w. 2003.

Harper’s Illustrated Biochemistry. Harper’s Illustrated Biochemistry. 2626th th Ed.Ed. Pratt,C.W.and Cornely K. 2004. Pratt,C.W.and Cornely K. 2004. Essential BiochemistryEssential Biochemistry. Wiley . Wiley

International Edition.International Edition. Stryer, Lubert 1995. Biochemistry.4th Stryer, Lubert 1995. Biochemistry.4th EdEd..

AndrogenAndrogen AndrogenAndrogen is the generic term for any natural or synthetic is the generic term for any natural or synthetic

compound, usually a compound, usually a steroid hormonesteroid hormone, that stimulates or , that stimulates or controls the development and maintenance of controls the development and maintenance of masculine masculine characteristicscharacteristics in in vertebrates vertebrates by binding to by binding to androgen receptorsandrogen receptors..

This includes the activity of the accessory This includes the activity of the accessory male sex organs male sex organs and and development of male development of male secondary sex characteristicssecondary sex characteristics..

Androgens, which were first discovered in Androgens, which were first discovered in 19361936, are also called , are also called androgenic hormonesandrogenic hormones or or testoidstestoids. .

Androgens are also the original Androgens are also the original anabolic steroidsanabolic steroids. They are also . They are also the precursor of all the precursor of all estrogensestrogens, the , the female female sex hormones. The sex hormones. The primary and most well-known androgen is primary and most well-known androgen is testosteronetestosterone..

The principal androgens are testosterone and androstenedione. The principal androgens are testosterone and androstenedione. They are, of course, present in much higher levels in men and They are, of course, present in much higher levels in men and play an important role in male traits and play an important role in male traits and reproductive activity. reproductive activity.

Besides testosterone, other androgens include:Besides testosterone, other androgens include: Dehydroepiandrosterone Dehydroepiandrosterone (DHEA): a steroid hormone (DHEA): a steroid hormone

produced in the produced in the adrenal cortex adrenal cortex from from cholesterolcholesterol.. It is It is the primary precursor of natural the primary precursor of natural estrogens DHEA estrogens DHEA is is also called also called dehydroisoandrosterone dehydroisoandrosterone or or dehydroandrosterone.dehydroandrosterone.

Androstenedione Androstenedione (Andro): an androgenic steroid (Andro): an androgenic steroid produced by theproduced by the testes testes, , adrenal cortex adrenal cortex , and , and ovariesovaries. . While While androstenedionesandrostenediones are converted metabolically to are converted metabolically to testosteronetestosterone and other and other androgensandrogens, they are also the , they are also the parent structure of parent structure of estroneestrone. Use of androstenedione as . Use of androstenedione as an athletic or body building an athletic or body building supplementsupplement has been has been banned by the banned by the International Olympic CommitteeInternational Olympic Committee as as well as other sporting organizations. well as other sporting organizations.

AndrostenediolAndrostenediol: the steroid metabolite that is thought : the steroid metabolite that is thought to act as the main regulator of gonadotropin secretion. to act as the main regulator of gonadotropin secretion.

Androsterone: a chemical by-product created during Androsterone: a chemical by-product created during the breakdown of androgens, or derived from the breakdown of androgens, or derived from progesterone, that also exerts minor masculinising progesterone, that also exerts minor masculinising effects, but with one-seventh the intensity of effects, but with one-seventh the intensity of testosterone. It is found in approximately equal testosterone. It is found in approximately equal amounts in the plasma and urine of both males and amounts in the plasma and urine of both males and females. females.

Dihydrotestosterone (DHT): a metabolite of Dihydrotestosterone (DHT): a metabolite of testosterone, and a more potent androgen than testosterone, and a more potent androgen than testosterone in that it binds more strongly to androgen testosterone in that it binds more strongly to androgen receptors. It is produced in the adrenal cortex.receptors. It is produced in the adrenal cortex.

Androgen functionsAndrogen functions

aa. . Development of the maleDevelopment of the maleTestis formationTestis formationAndrogen productionAndrogen productionAndrogen effectsAndrogen effectsEarly regulationEarly regulation

b. b. SpermatogenesisSpermatogenesis

c. c. Inhibition of fat depositionInhibition of fat deposition

d. d. Muscle massMuscle mass

e. e. BrainBrain

PathwayPathway of androgens

Testosteron BiosynthesisTestosteron Biosynthesis

Like other Like other steroidsteroid hormones, testosterone is hormones, testosterone is derived from derived from cholesterolcholesterol. The largest amounts of . The largest amounts of testosterone are produced by the testosterone are produced by the testestestes in men. It in men. It is also synthesized in smaller quantities in women is also synthesized in smaller quantities in women by the by the thecalthecal cells cells of the of the ovariesovaries, by the , by the placentaplacenta, , as well as by the as well as by the zonazona reticularisreticularis of the of the adrenal cortexadrenal cortex in both sexes. in both sexes.

In the In the testestestes, testosterone is produced by the , testosterone is produced by the LeydigLeydig cells cells. The male . The male generative glandsgenerative glands also also contain contain SertoliSertoli cells cells which require testosterone for which require testosterone for spermatogenesisspermatogenesis. Like most hormones, . Like most hormones, testosterone is supplied to target testosterone is supplied to target tissuestissues in the in the bloodblood where much of it is where much of it is transportedtransported bound to a bound to a specific specific plasma proteinplasma protein, , sex hormone binding globulinsex hormone binding globulin (SHBG). (SHBG).

Pathway of Pathway of TestosteronTestosteronee Bios Biosyyntnthhesisesis

Dihydrotestosterone in Peripheral TissuesDihydrotestosterone in Peripheral Tissues

Testosterone is metabolized by two pathways. Testosterone is metabolized by two pathways. One involves oxidation at the 17 position, and the other One involves oxidation at the 17 position, and the other

involves reduction of the A ring double bond and the 3-involves reduction of the A ring double bond and the 3-ketone.ketone.

Metabolism by the first pathway occurs in many tissues, Metabolism by the first pathway occurs in many tissues, including liver, and produces 17-ketosteroids that are including liver, and produces 17-ketosteroids that are generally inactive or less active than the parent compound.generally inactive or less active than the parent compound.

Metabolism by the second pathway, which is less efficient, Metabolism by the second pathway, which is less efficient, occurs primarily in target tissues and produces the potent occurs primarily in target tissues and produces the potent metabolite dihydrotestosterone (DHT).metabolite dihydrotestosterone (DHT).

The most significant metabolic product of testosterone is The most significant metabolic product of testosterone is DHT, since in many tissues, including prostate, external DHT, since in many tissues, including prostate, external genitalia, and some areas of the skin,this is the active form of genitalia, and some areas of the skin,this is the active form of the hormone.the hormone.

The plasma content of DHT in the adult male is about The plasma content of DHT in the adult male is about one-tenth that of testosterone, and approximately 400 one-tenth that of testosterone, and approximately 400 μg of DHT is produced daily as compared with about 5 μg of DHT is produced daily as compared with about 5 mg of testosterone.mg of testosterone.

About 50–100 μg of DHT are secreted by the testes. About 50–100 μg of DHT are secreted by the testes. The rest is produced peripherally from testosterone in a The rest is produced peripherally from testosterone in a

reaction catalyzed by the NADPH-dependent reaction catalyzed by the NADPH-dependent 5-5-reductasereductase

Testosterone can thus be considered a prohormone, Testosterone can thus be considered a prohormone, since it is converted into a much more potent since it is converted into a much more potent compound (dihydrotestosterone) and since most of this compound (dihydrotestosterone) and since most of this conversion occurs outside the testes. conversion occurs outside the testes.

Some estradiol is formed from the peripheral Some estradiol is formed from the peripheral aromatization of testosterone, particularly in males.aromatization of testosterone, particularly in males.

EstrogenEstrogen Estrogens (alternative spellings: oestrogens) are a group Estrogens (alternative spellings: oestrogens) are a group

of of steroidsteroid compounds, named for their importance in the compounds, named for their importance in the estrous cycleestrous cycle, and functioning as the primary , and functioning as the primary femalefemale sex hormonesex hormone..

Estrogens are used as part of some Estrogens are used as part of some oral contraceptivesoral contraceptives, in , in estrogen replacement therapy of estrogen replacement therapy of postmenopausalpostmenopausal women, women, and in and in hormone therapyhormone therapy for transsexual women. for transsexual women.

Like all Like all steroid hormonessteroid hormones, estrogens readily , estrogens readily diffusediffuse across across the the cell membranecell membrane; inside the cell, they interact with ; inside the cell, they interact with estrogen receptorsestrogen receptors

A range of synthetic and natural substances have been A range of synthetic and natural substances have been identified that also possess estrogenic activity. Synthetic identified that also possess estrogenic activity. Synthetic substances of this kind are known as substances of this kind are known as xenoestrogensxenoestrogens, while , while natural plant products with estrogenic activity are called natural plant products with estrogenic activity are called phytoestrogensphytoestrogens. .

Types of estrogenTypes of estrogenThe three major naturally The three major naturally occurring estrogens in women occurring estrogens in women are are estradiolestradiol, , estriolestriol, and , and estroneestrone. In the body these are . In the body these are all produced from all produced from androgensandrogens through actions of through actions of enzymesenzymes.. From From menarchemenarche to to

menopause the primary menopause the primary estrogen is estrogen is 17β-estradiol17β-estradiol. .

In postmenopausal women In postmenopausal women more more estroneestrone is present is present than than estradiolestradiol. .

Estradiol is produced from Estradiol is produced from testosteronetestosterone and estrone and estrone from from androstenedioneandrostenedione. .

Estrone is weaker than Estrone is weaker than estradiol. estradiol.

Estriol

Estradiol

Estrone

Estrogens Estrogens FunctionsFunctions While estrogens are present in both men and women, they are

usually present at significantly higher levels in women of reproductive age.

They promote the development of female secondary sex characteristics, such as breasts, and are also involved in the thickening of the endometrium and other aspects of regulating the menstrual cycle.

Role in cancerAbout 80% of breast cancers, once established, rely on supplies of the hormone estrogen to grow: they are known as hormone-sensitive or hormone-receptor-positive cancers. Suppression of production in the body of estrogen is a treatment for these cancers.

In males estrogen regulates certain functions of the reproductive system important to the maturation of sperm and may be necessary for a healthy libido

Furthermore, there are several other structural changes induced by Furthermore, there are several other structural changes induced by estrogen, in addition to other functions. estrogen, in addition to other functions. Structural Structural

-- promote formation of female secondary sex characteristics promote formation of female secondary sex characteristics - accelerate accelerate heightheight growth growth - accelerate accelerate metabolismmetabolism (burn fat) (burn fat) - reduce reduce musclemuscle mass mass - stimulate stimulate endometrialendometrial growth growth - increase increase uterineuterine growth growth - maintenance of vessel and skin maintenance of vessel and skin - - reduce reduce bone bone resorptionresorption, increase bone formation , increase bone formation - - morphicmorphic change ( change (endomorphicendomorphic -> -> mesomorphicmesomorphic -> ->

ectomorphicectomorphic) ) Protein synthesis Protein synthesis

increase hepatic production of binding proteins increase hepatic production of binding proteins Coagulation Coagulation

increase circulating level of increase circulating level of factorsfactors, , antithrombinantithrombin III, III, plasminogenplasminogen

increase increase plateletplatelet adhesiveness adhesiveness

Lipid Lipid increase increase HDLHDL, , triglyceridetriglyceride, , heightheight growth growth decrease decrease LDLLDL, , fatfat depositition depositition

Fluid balance Fluid balance salt (salt (sodiumsodium) and water retention ) and water retention increase increase growth hormonegrowth hormone increase increase cortisolcortisol, , SHBGSHBG

Gastrointestinal tract Gastrointestinal tract reduce bowel motility reduce bowel motility increase cholesterol in increase cholesterol in bilebile

Melanin Melanin increase increase pheomelaninpheomelanin, reduce , reduce eumelanineumelanin

Cancer Cancer support support hormone-sensitivehormone-sensitive breast cancersbreast cancers

Lung function Lung function promotes lung function by supporting promotes lung function by supporting alveolialveoli (in rodents but (in rodents but

probably in humans)probably in humans)

Estrogen productionEstrogen production

Estrogen is produced primarily by developing Estrogen is produced primarily by developing folliclesfollicles in the ovaries, the in the ovaries, the corpus corpus luteumluteum, and the , and the placentaplacenta. . Follicle-stimulating hormoneFollicle-stimulating hormone (FSH) and (FSH) and luteinizingluteinizing hormone hormone (LH) stimulate the production of estrogen in (LH) stimulate the production of estrogen in the the ovariesovaries..

Some estrogens are also produced in smaller amounts Some estrogens are also produced in smaller amounts by other tissues such as the by other tissues such as the liverliver, , adrenal glandsadrenal glands, and , and the the breastsbreasts. These secondary sources of estrogen are . These secondary sources of estrogen are especially important in postmenopausal women. especially important in postmenopausal women.

Synthesis of estrogens starts in Synthesis of estrogens starts in theca theca internainterna cells in cells in the ovary, by the synthesis of androstenedione from the ovary, by the synthesis of androstenedione from cholesterolcholesterol..

Androstenedione is a substance of moderate Androstenedione is a substance of moderate androgenic activity. androgenic activity.

This compound crosses the This compound crosses the basal membranebasal membrane into the into the surrounding surrounding granulosagranulosa cells cells, where it is converted to , where it is converted to estrone or estradiol, either immediately or through estrone or estradiol, either immediately or through testosterone. testosterone.

The conversion of testosterone to estradiol, and of The conversion of testosterone to estradiol, and of androstenedione to estrone, is catalyzed by the androstenedione to estrone, is catalyzed by the enzyme enzyme aromatasearomatase. .

Estradiol levels vary through the menstrual cycle, Estradiol levels vary through the menstrual cycle, with levels highest just before with levels highest just before ovulationovulation

Pathway of Estrogen Biosynthesis

Synthesis ProgesteronSynthesis Progesteron

Progesterone, like all other Progesterone, like all other steroidsteroid hormoneshormones, is synthesized , is synthesized from from pregnenolonepregnenolone, a derivative of , a derivative of cholesterolcholesterol. .

This conversion takes place in two steps. This conversion takes place in two steps. The 3-The 3-hydroxylhydroxyl group is converted to a group is converted to a ketoketo group group the the double bonddouble bond is moved to C-4, from C-5. is moved to C-4, from C-5.

Progesterone is the precursor of the mineralocorticoid Progesterone is the precursor of the mineralocorticoid aldosteronealdosterone, and after conversion to , and after conversion to 17-hydroxyprogesterone17-hydroxyprogesterone (another natural progestogen) of (another natural progestogen) of cortisolcortisol and and androstenedioneandrostenedione. Androstenedione can be converted to . Androstenedione can be converted to testosteronetestosterone, , estroneestrone and and estradiolestradiol. .

Pathway of Progesterone Biosynthesis

Progesterone is important for Progesterone is important for aldosteronealdosterone ( (mineralocorticoidmineralocorticoid) ) synthesis, as synthesis, as 17-hydroxyprogesterone17-hydroxyprogesterone is for is for cortisolcortisol ( (glucocorticoidglucocorticoid), and ), and androstenedioneandrostenedione for for sex steroidssex steroids

Female InfertilityFemale Infertility DDefine infertility as a couple not able to conceive at the end of efine infertility as a couple not able to conceive at the end of

two years of adequate opportunities two years of adequate opportunities Infertility describes a person's biological inability to contribute to Infertility describes a person's biological inability to contribute to

conception. Infertility can also describe a woman's inability to conception. Infertility can also describe a woman's inability to carry a pregnancy to full term. carry a pregnancy to full term.

CausesCauses: : Anovulation: this means failure on the part of the ovary to produce ova Anovulation: this means failure on the part of the ovary to produce ova

(egg). Frequently the common reasons are cyst in ovary, (egg). Frequently the common reasons are cyst in ovary, hypothyroidismhypothyroidism, , hormonal disturbances, some sex chromosome disorders and advanced age. hormonal disturbances, some sex chromosome disorders and advanced age.

Tubal Factor: bilateral tubal obstruction accounts for nearly 10% of cases. Tubal Factor: bilateral tubal obstruction accounts for nearly 10% of cases. Tuberculosis, other infections, appendix, or previous operations can distort Tuberculosis, other infections, appendix, or previous operations can distort and occlude the tubes. and occlude the tubes.

Uterine Factors: Tuberculosis, fibroids, or inadequately formed Uterine Factors: Tuberculosis, fibroids, or inadequately formed endometrium lining of the uterus. endometrium lining of the uterus.

Cervical Factors: cervical mucous hostility can obstruct the accent of Cervical Factors: cervical mucous hostility can obstruct the accent of sperm, thus causing infertility. sperm, thus causing infertility.

Coital errors, use of lubricants, improper timing, anxiety. Coital errors, use of lubricants, improper timing, anxiety.

Luteal phase deficienciesLuteal phase deficiencies can be caused by abnormal can be caused by abnormal follicle development or abnormal luteinization. follicle development or abnormal luteinization.

In both of these situations, the corpus luteum in the ovary In both of these situations, the corpus luteum in the ovary follicle does not generate enough progesterone. Normally, follicle does not generate enough progesterone. Normally, the corpus luteum in the ovary the corpus luteum in the ovary luteinizing hormoneluteinizing hormone (LH). (LH).

LH causes the body to produce progesterone producesLH causes the body to produce progesterone produces; a ; a hormone which causes the thickening of the blood vessels hormone which causes the thickening of the blood vessels in the uteral lining. in the uteral lining.

These blood vessels form a protective, nourishing network, These blood vessels form a protective, nourishing network, where the fertilized egg can develop into a baby. where the fertilized egg can develop into a baby.

A lack of progesterone causes the blood vessel network to A lack of progesterone causes the blood vessel network to weaken and drop out of the uterine, ending the pregnancy. weaken and drop out of the uterine, ending the pregnancy.

This is similar to what happens in a normal monthly period, This is similar to what happens in a normal monthly period, when there is no pregnancy.when there is no pregnancy.

Luteal Phase deficiency (LPD)Luteal Phase deficiency (LPD)

LPDLPD is found in 3-20% of patients who are infertile and in is found in 3-20% of patients who are infertile and in 5-60% of patients who experience recurrent pregnancy 5-60% of patients who experience recurrent pregnancy lossloss. However, data show that 6-10% of women who are . However, data show that 6-10% of women who are fertile also have an inadequate luteal phase.fertile also have an inadequate luteal phase.

Luteal Phase Defect - In a luteal phase defect, a woman's Luteal Phase Defect - In a luteal phase defect, a woman's corpus luteum - the mound of yellow tissue produced from corpus luteum - the mound of yellow tissue produced from the egg follicle - may fail to produce enough progesterone the egg follicle - may fail to produce enough progesterone to thicken the uterine lining. Then the fertilized egg may be to thicken the uterine lining. Then the fertilized egg may be unable to implant. unable to implant.

Medications - Many medicines, such as hormones, Medications - Many medicines, such as hormones, antibiotics, antidepressants, and pain killers may bring on antibiotics, antidepressants, and pain killers may bring on temporary infertility. Commonly used medications such as temporary infertility. Commonly used medications such as aspirin and ibuprofen can also impair fertility if taken mid-aspirin and ibuprofen can also impair fertility if taken mid-cycle. Acetaminophen (Tylenol) pills can reduce the cycle. Acetaminophen (Tylenol) pills can reduce the amount of estrogen and luteinizing hormones in the body, amount of estrogen and luteinizing hormones in the body, impairing fertility. impairing fertility.

Human chorionic gonadotropin (hCG) is similar to LH; it contains equal amounts of LH and FSH. These hormones play a central role in egg production.

In women. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are necessary for egg production (ovulation). Early in the menstrual cycle, a woman with low hormone levels who is not ovulating can have daily human menopausal gonadotropin (hMG) or recombinant human FSH (rFSH) injections for an average of 12 days. If this helps develop mature follicles, the ovary is ready to ovulate. One dose of human chorionic gonadotropin (hCG) is then used to stimulate ovulation.

The gonadotropin secretory pattern of anorexia nervosa The gonadotropin secretory pattern of anorexia nervosa patients is similar to the prepubertal pattern. patients is similar to the prepubertal pattern.

When gonadotropin-releasing hormone (GnRH) is When gonadotropin-releasing hormone (GnRH) is administered to patients with 53%-64% of their ideal body administered to patients with 53%-64% of their ideal body weight (IBW), they have a weak luteinizing hormone (LH) weight (IBW), they have a weak luteinizing hormone (LH) response and a normal follicle-stimulating hormone (FSH) response and a normal follicle-stimulating hormone (FSH) response. response.

As their weight increases, the LH response becomes As their weight increases, the LH response becomes stronger, and at 90%-94% of their IBW, the LH response is stronger, and at 90%-94% of their IBW, the LH response is frequently exaggerated. frequently exaggerated.

Other studies indicate that an exaggerated LH response also Other studies indicate that an exaggerated LH response also occurs when GnRH is administered to fashionably slim occurs when GnRH is administered to fashionably slim women women

GonadotropinGonadotropin

In women gonadotropins may be used :In women gonadotropins may be used :To stimulate ovulation related to low natural To stimulate ovulation related to low natural

gonadotropin or estrogen levels. (This is most gonadotropin or estrogen levels. (This is most commonly seen in women with excessive exercise or commonly seen in women with excessive exercise or eating disorders.) eating disorders.)

Clomiphene and metformin have been ineffective for Clomiphene and metformin have been ineffective for correcting irregular or no ovulation caused by polycystic correcting irregular or no ovulation caused by polycystic ovary syndrome (PCOS). ovary syndrome (PCOS).

For developing multiple egg follicles on the ovaries. For developing multiple egg follicles on the ovaries. Multiple eggs are harvested and used in assisted Multiple eggs are harvested and used in assisted reproductive techniques such as in vitro fertilization or reproductive techniques such as in vitro fertilization or gamete intrafallopian transfer. gamete intrafallopian transfer.

In combination with intrauterine insemination for In combination with intrauterine insemination for couples with unexplained infertility when clomiphene couples with unexplained infertility when clomiphene has not worked.has not worked.

THYROID DYSFUNCTION IN INFERTILE WOMEN

Thyroid is an important endocrine gland and its dysfunctions interfere with numerous aspects of reproduction and pregnancy

Thyroid hormones receptors and their mRNA have been detected in human granulosa cells and direct effects of iodine and thyroid hormone on ovarian function are proposed recently.

There is a known association of hyperthyroidism and hypothyroidism with menstrual disturbance, anovulatory cycles and decreased fecundity.

A number of studies have high lighted the role of thyroid dysfunction in female infertility hypothalamic-pituitary-thyroid axis in such infertile women is less sensitive and they had compensated thyroid hormone profile with tissue hypothyroidism.

Such thyroid under function can affect female

reproductive physiology indirectly in a number of ways: altering the pituitaryovarian axis, decreasing the binding activity of sex hormone binding globulin (SHBG) resulting in increased serum-free testosterone and estradiol, decreasing the metabolic clearance of androstenedione and estrone and increasing TRH levels resulting in increased prolactin levels and a delayed LH response to LH-releasing hormone.

The higher conception rate after thyroxine supplementation in infertile women with increased TSH verifies the presence of tissue hypothyroidism in such women

Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH level below 2.5 mIU/L.

In a comparison of infertile women with different females, the reasons of infertility has revealed that ovulatory dysfunction is particularly associated with hypothyroidism and increased TSH levels

HHyperprolactinemiayperprolactinemia Excessive secretion of prolactin - Excessive secretion of prolactin - hyperprolactinemiahyperprolactinemia - is a - is a

relatively common disorder in humans. This condition has relatively common disorder in humans. This condition has numerous causes, including prolactin-secreting tumors and numerous causes, including prolactin-secreting tumors and therapy with certain drugs. therapy with certain drugs.

Common manifestations of hyperprolactinemia in women Common manifestations of hyperprolactinemia in women include amenorrhea (lack of menstrural cycles) and include amenorrhea (lack of menstrural cycles) and galactorrhea (excessive or spontaneous secretion of milk). galactorrhea (excessive or spontaneous secretion of milk).

Hyperprolactinemic states result in hypogonadism through inhibition of gonadotropin secretion and suppression of gonadal steroidogenesis.

Anovulation usually results when immunoreactive prolactin concentrations exceed 60 pg/L, but ovulatory cycles can persist in about 5% of hyperprolactinemic women, because the prolactin's biologic action in the circulation differs from its immunologic action.

Regulating prolactin secretion

Normal levels of prolactin range between 5 and 27 μg/L(580 mIU/L) for women and between 5 and 15 μ g/L (450 mIU/L) for men.

During pregnancy, levels rise; at term, mean maternal and umbilical cord plasma concentrations reach approximately 200 to 250 μg/L.

The prevalence of a prolactinoma is about 60% in women with prolactin levels higher than 100 μg/L, and very high with prolactin levels higher than 250 μg/L.

Most of these are microadenomas (lesions less than 10 mm in diameter).

The increase is a result of estrogen-induced hyperplasia of the lactotropes (the prolactin-secreting cells) in the pituitary gland.

The hypothalamus has an inhibitory action on prolactin release from the pituitary, mediated by a prolactin-inhibiting factor (PIF).

The hormone prolactin is downregulated by dopamine and is upregulated by estrogen.

Dopamine agonists (bromocriptine, levodopa, apomorphine) inhibits prolactin release;

Dopamine receptor antagonists (phenothiazines, metoclopramide, pimozide) stimulate prolactin release

There is a high incidence of hyperprolactinemia in infertile women.

A positive correlation of 1:4 was found between hypothyroidism and hyperprolactinemia.

Polycystic Ovary Syndrome Polycystic Ovary Syndrome (Stein-Leventhal Syndrome) (Stein-Leventhal Syndrome)

Polycystic ovary syndrome (PCOS) is a hormone disorder Polycystic ovary syndrome (PCOS) is a hormone disorder that causes many small benign cyststhat causes many small benign cysts to form on the ovariesto form on the ovaries under a thick, white covering, which under a thick, white covering, which prevents the release of an prevents the release of an egg. egg.

It causes your It causes your menstrual cycle to be irregularmenstrual cycle to be irregular, or you may , or you may have no periods at allhave no periods at all. . PCOS can make it hard for you to PCOS can make it hard for you to become pregnant become pregnant

The two ovaries are part of the female reproductive systemThe two ovaries are part of the female reproductive system, , they produce eggs and the female hormonesthey produce eggs and the female hormones estrogen and estrogen and progesterone. progesterone.

Ovarian cysts are fluid-filled sacs that form on the ovaries when Ovarian cysts are fluid-filled sacs that form on the ovaries when the follicles (sacs) on the ovary that contain an egg mature but the follicles (sacs) on the ovary that contain an egg mature but do not release the egg into the fallopian tube. do not release the egg into the fallopian tube.

Some women with polycystic ovary syndrome may have mildly-Some women with polycystic ovary syndrome may have mildly-elevated prolactin levels. elevated prolactin levels.

PCOS increases your risk of uterine cancer, diabetes, and heart PCOS increases your risk of uterine cancer, diabetes, and heart disease disease

It is the most common cause of infertility, occurring in about ten It is the most common cause of infertility, occurring in about ten percent of all women.percent of all women.

The main symptoms include irregular ovulation and/or The main symptoms include irregular ovulation and/or menstruation, weight problems, and too many masculine menstruation, weight problems, and too many masculine hormones.hormones.

Irregular ovulation means that often there will not be eggs to be Irregular ovulation means that often there will not be eggs to be impregnated. impregnated.

Menstruation problems cause an actual pregnancy not to last. Menstruation problems cause an actual pregnancy not to last. While the causes of PCOS are not known, obesity, diabetes and While the causes of PCOS are not known, obesity, diabetes and insulin resistance often accompany PCOS.insulin resistance often accompany PCOS.

Many physicians miss this, so one should search for a physician Many physicians miss this, so one should search for a physician who is experienced with this. For overweight women, weight who is experienced with this. For overweight women, weight loss can improve the conditionloss can improve the condition

How does PCOS occurHow does PCOS occur

Studies are looking at whether it is caused by Studies are looking at whether it is caused by genetics. genetics. AAlso, because many women with PCOS also have diabetes, lso, because many women with PCOS also have diabetes,

studies are examining the relationship between PCOS and studies are examining the relationship between PCOS and the level of insulin in the body.the level of insulin in the body.

High levels of insulin appear to cause the body to make High levels of insulin appear to cause the body to make more of the male hormone testosterone, which worsens the more of the male hormone testosterone, which worsens the symptoms of PCOS. symptoms of PCOS.

A problem called insulin resistance (inefficient use of A problem called insulin resistance (inefficient use of insulin in the body) can cause the high levels of insulin. Too insulin in the body) can cause the high levels of insulin. Too much insulin in the body increases the risk for other much insulin in the body increases the risk for other problems, such as obesity, diabetes, high blood pressure, problems, such as obesity, diabetes, high blood pressure, and heart disease. and heart disease.

The PCOS symptoms include:The PCOS symptoms include:

Irregular menstrual periods, particularly long Irregular menstrual periods, particularly long cycles, or no periods at all cycles, or no periods at all Very light or very heavy bleeding during your Very light or very heavy bleeding during your

period period Trouble getting pregnant Trouble getting pregnant More hair on your face, chest, and lower More hair on your face, chest, and lower

abdomen abdomen Balding in some women Balding in some women Obesity Obesity Acne. Acne.

Hydatidiform moleHydatidiform moleMolar pregnancyMolar pregnancy is an abnormal form of is an abnormal form of pregnancypregnancy, , characterized by the presence of a characterized by the presence of a hydatidiform molehydatidiform mole (or (or hydatid molehydatid mole, , mola hytadidosamola hytadidosa), an anomalous growth ), an anomalous growth containing a nonviable containing a nonviable embryo embryo which implants and proliferates which implants and proliferates within the within the uterus. uterus. A hydatidiform mole is removed upon A hydatidiform mole is removed upon diagnosis because there is some risk that it develop into diagnosis because there is some risk that it develop into choriocarcinomachoriocarcinoma, a form of cancer. , a form of cancer.

A hydatidiform mole is a pregnancy/conceptus in which the A hydatidiform mole is a pregnancy/conceptus in which the placenta contains grapelike vesicles that are visible with the placenta contains grapelike vesicles that are visible with the naked eye naked eye

The vesicles arise by distention of the chorionic villi by fluid. The vesicles arise by distention of the chorionic villi by fluid. When inspected in the microscope, hyperplasia of the When inspected in the microscope, hyperplasia of the trophoblastic tissue is noted. If left untreated, a hydatidiform trophoblastic tissue is noted. If left untreated, a hydatidiform mole always ends as a spontaneous abortion. mole always ends as a spontaneous abortion.

Potential risk factors may include defects in the egg, Potential risk factors may include defects in the egg, abnormalities within the uterus, or nutritional deficiencies. abnormalities within the uterus, or nutritional deficiencies. Women under 20 or over 40 years of age have a higher risk. Women under 20 or over 40 years of age have a higher risk. Other risk factors include diets low in protein, folic cid, and Other risk factors include diets low in protein, folic cid, and carotene carotene The diploid set of sperm-only DNA means that all The diploid set of sperm-only DNA means that all chromosomes have sperm-patterned methylationchromosomes have sperm-patterned methylation suppression suppression of genes.of genes. This leads to overgrowth of the syncytiotrophoblast whereas This leads to overgrowth of the syncytiotrophoblast whereas dual egg-patterned methylation leads to a devotion of resources dual egg-patterned methylation leads to a devotion of resources to the embryo, with an underdeveloped syncytiotrophoblast. to the embryo, with an underdeveloped syncytiotrophoblast. This is considered to be the result of evolutionary competition This is considered to be the result of evolutionary competition with male genes driving for high investment into the fetus with male genes driving for high investment into the fetus versus female genes driving for resource restriction to versus female genes driving for resource restriction to maximise the number of children maximise the number of children

Treatment of Hydatidiform moleTreatment of Hydatidiform mole

HHydatidiform moles should be treated by evacuating the uterus ydatidiform moles should be treated by evacuating the uterus by uterine suction or by surgical by uterine suction or by surgical curettagecurettage as soon as possible as soon as possible after diagnosis, in order to avoid the risks of after diagnosis, in order to avoid the risks of choriocarcinomachoriocarcinoma..Patients are followed up until their serum human chorionic Patients are followed up until their serum human chorionic gonadotrophin (hCG) level has fallen to an undetectable level. gonadotrophin (hCG) level has fallen to an undetectable level. Invasive or metastatic moles (cancer) may require chemotherapy Invasive or metastatic moles (cancer) may require chemotherapy and often respond well to methotrexate. and often respond well to methotrexate. The response to treatment is nearly 100%. Patients are advised The response to treatment is nearly 100%. Patients are advised not to conceive for one year after a molar not to conceive for one year after a molar pregnancy. The chances of having another molar pregnancy are pregnancy. The chances of having another molar pregnancy are approximately 1%.approximately 1%.Management is more complicated when the mole occurs together Management is more complicated when the mole occurs together with one or more normal fetuses.with one or more normal fetuses.

Turner syndrome or Ullrich-Turner syndrome encompasses several Turner syndrome or Ullrich-Turner syndrome encompasses several conditions, of which conditions, of which monosomy monosomy XX is the most common. It occurs is the most common. It occurs in about 1 out of every 2500 female births.in about 1 out of every 2500 female births.Instead of the normal XX Instead of the normal XX sex chromosomes sex chromosomes for a female, only one for a female, only one X chromosome X chromosome is present and fully functional; in rarer cases a is present and fully functional; in rarer cases a second second X chromosome is present but abnormalX chromosome is present but abnormal, while others , while others with the condition have some cells with a second X and other cells with the condition have some cells with a second X and other cells without it (without it (mosaicism)mosaicism). . A normal female A normal female karyotype karyotype is labis labeeled 46,XX; individuals with led 46,XX; individuals with Turner syndrome are 45,X. Turner syndrome are 45,X. In Turner syndrome, female sexual characteristics are present but In Turner syndrome, female sexual characteristics are present but generally underdeveloped. generally underdeveloped. Nearly all girls with Nearly all girls with Turner syndrome will be infertileTurner syndrome will be infertile, or , or unable unable to become pregnantto become pregnant on their own. on their own.

Turner syndromeTurner syndrome

Other eOther effects Can Turner Syndrome Haveffects Can Turner Syndrome Have:: Kidney problems, Kidney problems, High blood pressure,High blood pressure, heart problems, heart problems, overweight,overweight, hearing difficulties, hearing difficulties, Diabetes, cataracts, Diabetes, cataracts, Tyroid promlems.Tyroid promlems. Some girls with the condition may experience learning Some girls with the condition may experience learning

difficulties, particularly in math. difficulties, particularly in math. Many have a difficult time with tasks that require skills Many have a difficult time with tasks that require skills

such as map reading or visual organization. such as map reading or visual organization.

How Is Turner Syndrome TreatedHow Is Turner Syndrome Treated

Growth hormoneGrowth hormone treatment can improve growth and influence a girl's treatment can improve growth and influence a girl's final adult height. In fact, in many cases, the treatment can help many final adult height. In fact, in many cases, the treatment can help many girls with Turner syndrome reach a final height in the average range, girls with Turner syndrome reach a final height in the average range, especially if treatment is started early enough especially if treatment is started early enough Another treatment for Turner syndrome is Another treatment for Turner syndrome is estrogen replacementestrogen replacement, which , which helps the girl develop the physical changes of pubertyhelps the girl develop the physical changes of puberty (12-13 years old) (12-13 years old), , including breast growth and eventually menstrual periods. including breast growth and eventually menstrual periods. And a technique called And a technique called in vitroin vitro fertilization fertilization can make it possible for can make it possible for some women with Turner syndrome to become pregnant. some women with Turner syndrome to become pregnant. A donor egg A donor egg can be used to create an embryo, which is then put into the uterus can be used to create an embryo, which is then put into the uterus (womb) of the woman with Turner syndrome. With proper (womb) of the woman with Turner syndrome. With proper supportive care, the woman can carry the pregnancy to term and supportive care, the woman can carry the pregnancy to term and deliver a baby through the normal birth process.deliver a baby through the normal birth process.Girls with Turner syndrome are usually short in height. Girls with Girls with Turner syndrome are usually short in height. Girls with Turner syndrome who aren't treated reach an average height of about 4 Turner syndrome who aren't treated reach an average height of about 4 feet 7 inches (1.4 meters). The good news is that when Turner syndrome feet 7 inches (1.4 meters). The good news is that when Turner syndrome is diagnosed while a girl is still growing, she can be treated with is diagnosed while a girl is still growing, she can be treated with hormones to help her grow taller. hormones to help her grow taller.

Common symptoms of Turner syndrome include:

Short stature Short stature LymphoedemaLymphoedema (swelling) of the hands and feet (swelling) of the hands and feet Broad chest (Broad chest (shield chestshield chest) and widely-spaced nipples ) and widely-spaced nipples Low hairline Low hairline Low-set ears Low-set ears Reproductive sterility Reproductive sterility (infertility)(infertility) Rudimentary ovaries gonadal streak (underdeveloped gonadal structures) Rudimentary ovaries gonadal streak (underdeveloped gonadal structures) AmenorrheaAmenorrhea,, or the absence of a menstrual period or the absence of a menstrual period Increased weight,Increased weight, obesity obesity Shield shaped thorax of heart Shield shaped thorax of heart Shortened Shortened metacarpal IVmetacarpal IV (of hand) (of hand) Small fingernails Small fingernails Characteristic facial features Characteristic facial features Webbing of the neck (Webbing of the neck (webbed neckwebbed neck) ) CoarctationCoarctation of the of the aortaaorta Poor breast development Poor breast development Horseshoe kidneyHorseshoe kidney Visual impairments Visual impairments sclerasclera, , corneacornea, , GlaucomaGlaucoma, Drooping eyelids, Drooping eyelids, , Dry eyes Dry eyes Ear infections and hearing loss. Ear infections and hearing loss.

Risk factorsRisk factors

Risk factors for Turner syndrome are not well known. Risk factors for Turner syndrome are not well known. Nondisjunctions increase with maternal age, such as Nondisjunctions increase with maternal age, such as for for Down syndromeDown syndrome, but that effect is not clear for , but that effect is not clear for Turner syndrome. Turner syndrome. It is also unknown if there is a genetic predisposition It is also unknown if there is a genetic predisposition present that causes the abnormality, though most present that causes the abnormality, though most researchers and doctors treating Turners women agree researchers and doctors treating Turners women agree that this is highly unlikely. that this is highly unlikely. There is currently no known cause for Turner There is currently no known cause for Turner syndrome, though there are several theories syndrome, though there are several theories surrounding the subject. surrounding the subject.

TTurner syndrome because the number of individuals studied urner syndrome because the number of individuals studied within the less common karyotype groups is too small.within the less common karyotype groups is too small.Other studies also suggest the presence of hidden mosaicisms Other studies also suggest the presence of hidden mosaicisms that are not diagnosed on usual karyotypic analyses in some that are not diagnosed on usual karyotypic analyses in some patients with 45,X karyotype. patients with 45,X karyotype.

Thyroid disease is interrelated with women's hormones, and Thyroid disease is interrelated with women's hormones, and can have an impact on menstrual cycles, fertility, can have an impact on menstrual cycles, fertility, estrogen/progesterone levels, successful pregnancy, and the estrogen/progesterone levels, successful pregnancy, and the ability to breastfeed and menopause. ability to breastfeed and menopause.

Hypothyroidism in pregnancy can have adverse effects for the Hypothyroidism in pregnancy can have adverse effects for the child's development child's development

Thyroid problems after pregnancy occur in as many as 10 Thyroid problems after pregnancy occur in as many as 10 percent of all new mothers. percent of all new mothers.

Cause of Turner syndrome Cause of Turner syndrome

INFERTILITY IN MENINFERTILITY IN MEN A variety of disorders ranging from A variety of disorders ranging from hormonal disturbanceshormonal disturbances

to physical problems, to psychological problems can to physical problems, to psychological problems can cause cause male infertility.  male infertility. 

Although many treatment options are now available, in many Although many treatment options are now available, in many cases treatment will not work.  In many instances, male cases treatment will not work.  In many instances, male infertility is caused by testicular damage resulting in an infertility is caused by testicular damage resulting in an inability of the testicle to produce sperm.  inability of the testicle to produce sperm. 

Once damaged, the testicle will not usually regain its sperm-Once damaged, the testicle will not usually regain its sperm-making capabilities; this aspect of male infertility is making capabilities; this aspect of male infertility is analogous to menopause (though not natural like menopause) analogous to menopause (though not natural like menopause) for women and cannot usually be treated.  for women and cannot usually be treated. 

Despite medicine’s limited ability to treat male infertility, Despite medicine’s limited ability to treat male infertility, many successful treatment options are available for its many many successful treatment options are available for its many causes. causes. 

Besides testicular damage, the main causes of male Besides testicular damage, the main causes of male infertility are infertility are low sperm production and poor sperm quality. low sperm production and poor sperm quality.

Endocrine evaluation includes measurement of follicle stimulating hormone (FSH) and testosterone.Luteinizing hormone (LH), estradiol,and prolactin are also commonly measured.

The function of the testes is dependent upon hormones from the pituitarygland - follicle stimulating hormone (FSH) and luteinizing hormone (LH).

The levels of these hormones rises during the early stages of puberty and stimulates testicular development.

LH controls production of the male sex hormone testosterone which in turn is responsible for development of the genitals, beard and body hair, prostate and seminal vesicles, and also bone and muscle development and other aspects of masculine physique.

If LH and FSH are deficient the testes do not develop properly.

In contrast, if the testes are damaged directly, the levels of these hormones in the blood rise. Thus the measurement of LH, FSH and testosterone in blood helps in the diagnosis of testicular disorders.

Deficiency of two hormones from the pituitary gland, LH and FSH, can be treated by injection or hormone preparations.

In men with low testosterone and FSH, LH stimulates the production of testosterone, and FSH promotes the formation of sperm. If a semen analysis, LH, and FSH testing suggest that abnormal hormone levels are preventing sperm production, these gonadotropins may be prescribed to promote sperm formation together.

hCG (Human chorionic gonadotropin) ) is injected 3 times weekly until blood testosterone level is within the normal range (this may take 4 to 6 months).

Treatment continues with injections of hCG twice a week and hMG or FSH 3 times a week until the sperm count rises to normal levels.

Rarely, a hormonal difficulty that decreases or stops the man's production of sperm. Hormonal problems may be present from birth or can develop from brain or pituitary gland tumors or radiation treatment. Sometimes, hormonal difficulties are induced by excessive exercise, malnutrition or other illnesses

Hormone-sensitive lipase (HSL)

The 84-kDa hormone-sensitive lipase (gene designation Lipe; EC 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, hormone-sensitive lipase deficiency results in abnormalities in spermiogenesis that are incompatible with normal fertility

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters (CEs). The enzyme of acylglycerols and cholesteryl esters (CEs). The enzyme is highly expressed in adipose tissues (ATs), where it is is highly expressed in adipose tissues (ATs), where it is thought to play an important role in fat mobilization. thought to play an important role in fat mobilization.

The Causes of Male InfertilityThe Causes of Male Infertility

Male infertility has many causes-fromMale infertility has many causes-from: : hormonal imbalanceshormonal imbalancesphysical problems, physical problems, psychological and/or behavioral problems. psychological and/or behavioral problems. 

Moreover, fertility reflects a man’s “overall” health. Men Moreover, fertility reflects a man’s “overall” health. Men who live a healthy lifestyle are more likely to produce who live a healthy lifestyle are more likely to produce healthy sperm.  healthy sperm. 

Modifying these behaviors can improve a man’s fertility Modifying these behaviors can improve a man’s fertility and should be considered when a couple is trying to and should be considered when a couple is trying to achieve pregnancy.achieve pregnancy.

SSome lifestyle choices that negatively impact male fertilityome lifestyle choices that negatively impact male fertility it is not it is not all-inclusive: all-inclusive:

· · SmokingSmoking s significantly decreases both sperm count and sperm ignificantly decreases both sperm count and sperm cell motility. cell motility.

· · Prolonged use of marijuana and other recreational drugs. Prolonged use of marijuana and other recreational drugs. · · Chronic alcohol abuse. Chronic alcohol abuse. · · Anabolic steroid use--causes testicular shrinkage and infertility. Anabolic steroid use--causes testicular shrinkage and infertility.

· · Overly intense exerciseOverly intense exercise produces high levels of adrenal produces high levels of adrenal steroid hormones which cause a testosterone deficiencysteroid hormones which cause a testosterone deficiency resulting in infertility. resulting in infertility. ·· Inadequate vitamin C and Zinc in the diet. Inadequate vitamin C and Zinc in the diet. ·· Tight underwear Tight underwear increases scrotal temperature which results in increases scrotal temperature which results in

decreased sperm production. decreased sperm production. ·· Exposure to environmental hazards and toxins such as Exposure to environmental hazards and toxins such as pesticides, lead, paint, radiation, radioactive substances, pesticides, lead, paint, radiation, radioactive substances, mercury, benzene, boron, and heavy metals mercury, benzene, boron, and heavy metals · · Malnutrition and anemia. Malnutrition and anemia. · · Excessive stress! Excessive stress!

Hormonal Problems Hormonal Problems A small percentage of male infertility is caused by hormonal problems. A small percentage of male infertility is caused by hormonal problems.  The hypothalamus-pituitary endocrine system regulates the chain of The hypothalamus-pituitary endocrine system regulates the chain of

hormonal events that enables testes to produce and effectively hormonal events that enables testes to produce and effectively disseminate sperm. disseminate sperm. 

Several things can go wrong with the hypothalamus-pituitary endocrine Several things can go wrong with the hypothalamus-pituitary endocrine system:system: The brain can fail to release gonadotrophic-releasing hormone The brain can fail to release gonadotrophic-releasing hormone

(GnRH) properly. GnRH stimulates the hormonal pathway that (GnRH) properly. GnRH stimulates the hormonal pathway that causes testosterone synthesis and sperm production.  A disruption in causes testosterone synthesis and sperm production.  A disruption in GnRH release leads to a lack of testosterone and a cessation in sperm GnRH release leads to a lack of testosterone and a cessation in sperm productionproduction. .

The pituitary can fail to produce enough The pituitary can fail to produce enough lutenizing hormonelutenizing hormone (LH) and (LH) and follicle stimulating hormonefollicle stimulating hormone (FSH) to stimulate the testes and (FSH) to stimulate the testes and testosterone/sperm production. LH and FSH are intermediatestestosterone/sperm production. LH and FSH are intermediates in the in the hormonal pathway responsible for testosterone and sperm production. hormonal pathway responsible for testosterone and sperm production.

The testes’ Leydig cells may not produce testosterone in response to LH The testes’ Leydig cells may not produce testosterone in response to LH stimulation. stimulation.

A male may produce other hormones and chemical compounds which A male may produce other hormones and chemical compounds which interfere with the sex-hormone balance. interfere with the sex-hormone balance.

HHormonal disorders which can disrupt ormonal disorders which can disrupt male infertility: male infertility:

1.1. HyperprolactinemiaHyperprolactinemia

2.2. HypothyroidismHypothyroidism

3.3. Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia

4.4. Hypogonadotropic HypopituitarismHypogonadotropic Hypopituitarism

5.5. PanhypopituitarismPanhypopituitarism

1. Hyperprolactinemia:1. Hyperprolactinemia: • Elevated prolactin-a hormone associated with nursing Elevated prolactin-a hormone associated with nursing mothers, mothers, is found in 10 to 40 percent of is found in 10 to 40 percent of infertile males infertile males • Mild elevation of prolactin levels produces no symptoms, but Mild elevation of prolactin levels produces no symptoms, but

greater elevations of the hormone greater elevations of the hormone reduces sperm reduces sperm productionproduction, , reduces libido and may cause impotence.  reduces libido and may cause impotence.  • This condition responds well to the drug Parlodel This condition responds well to the drug Parlodel (bromocriptine). (bromocriptine). • Men with Men with hyperprolactinemia typically show hyperprolactinemia typically show hypogonadism, hypogonadism, with decreased sex drive, decreased with decreased sex drive, decreased sperm production and sperm production and impotence. impotence. • Such men also often show breast enlargement (Such men also often show breast enlargement (gynecomastiagynecomastia), ),

but very rarely produce milk.but very rarely produce milk.

2.2. HypothyroidismHypothyroidism:: Low thyroid hormone levelsLow thyroid hormone levels can cause poor semen quality, can cause poor semen quality,

poor testicular function and may disturb libido.  poor testicular function and may disturb libido.  May be caused by a diet high in iodine. May be caused by a diet high in iodine. Reducing iodine intake or beginning thyroid hormone Reducing iodine intake or beginning thyroid hormone

replacement therapy can elevate sperm count.  replacement therapy can elevate sperm count.  This condition is found in only 1 percent of infertile men. This condition is found in only 1 percent of infertile men.

3.3. Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia:: Low thyroid hormone levelsLow thyroid hormone levels can cause poor semen quality, can cause poor semen quality,

poor testicular function and may disturb libido.  poor testicular function and may disturb libido.  May be caused by a diet highMay be caused by a diet high in iodine.  in iodine.  Reducing iodine intake or beginning thyroid hormone Reducing iodine intake or beginning thyroid hormone

replacement therapy can elevate sperm count.  replacement therapy can elevate sperm count.  This condition is found in This condition is found in only 1 percent of infertile men. only 1 percent of infertile men.

4.4. Hypogonadotropic Hypopituitarism:Hypogonadotropic Hypopituitarism: • Low pituitary gland output of LH and FSH. Low pituitary gland output of LH and FSH. • This condition arrests sperm development and causes the progressive loss This condition arrests sperm development and causes the progressive loss

of germ cells from the testes and causes the seminiferous tubules and of germ cells from the testes and causes the seminiferous tubules and Leydig (testosterone producing) cells to deteriorate. Leydig (testosterone producing) cells to deteriorate. 

• May be treated with the drug Serophene.  However, if all germ cells are May be treated with the drug Serophene.  However, if all germ cells are destroyed before treatment commences, destroyed before treatment commences, the male may be permanently the male may be permanently infertile. infertile.

5.5. Panhypopituitarism:Panhypopituitarism: • Complete pituitary gland failure--lowers growth hormone, thyroid-Complete pituitary gland failure--lowers growth hormone, thyroid-

stimulating hormone, and LH and FSH levelsstimulating hormone, and LH and FSH levels.  .  • Symptoms include:  lethargy, Symptoms include:  lethargy, impotence, decreased libido, loss of impotence, decreased libido, loss of

secondary sex characteristics, and normal or undersized testiclessecondary sex characteristics, and normal or undersized testicles . . • Supplementing the missing pituitary hormones may restore vigor and a Supplementing the missing pituitary hormones may restore vigor and a

hormone called hCG may stimulate testosterone and sperm production.hormone called hCG may stimulate testosterone and sperm production.